We have determined a role of chondrocyte mitochondrial oxidative phosphorylation (OXPHOS) in matrix synthesis and mineralizing activity. Chondrocyte respiration was inhibited by the NO donor Sin-1. Chondrocyte mitochondrial reserve, as OXPHOS-induced ATP production, supported matrix synthesis and basal and TGFbeta-induced Ppi elaboration, and regulated MV composition and mineralizing activity. Because altered chondrocyte OXPHOS could modulate matrix loss and secondary cartilage mineralization in osteoarthritis (OAO, we propose a limited feasibility study to first assess if experimental OA in rabbit knees can be studied for, and is associated with, mitochondrial OXPHOS impairment. We will also carry out a clinical pilot study to quantify OXPHOS (and identify OXPHOS impairment including deficiency of the mitochondrial protective agent coenzyme Q10 (CoQ10), on an existing panel of isolated primary chondrocytes from human knee OA. Results of this pilot project could determine if OXPHOS preservation is a therapeutic target in OA.